the endometrium and its pathology

Question 1

What are the points this lecture covers

Answer 1

Review normal function
Endometrial abnormalities including DUB
Clinical problems with real cases
Clinical management – related to patho-physiology

Question 2

What are the 4 layers of the endometrium

Answer 2

Compactum
Spongiosum
Basalis
Junctional zone

Question 3

How does menstruation happen

Answer 3

Initiated by withdrawal of E and P
Local mediators PG’s, PAF
Spiral artery vasoconstriction
				
Ischaemia and tissue damage
                           
Spiral artery relaxation
				
Shedding of functional endometrium

Control E2 + P
PGs (E + I vs F2a + Tx)
Interleukins (IL – 8, 13 +16)
Tissue Necrosis Factor (TNF) + Platelet Aggregating Factor (PAF)
Matrix metallo-proteinases
Coagulation / fibrinolysis
Junctional zone 

For normal menstruation:

Correct balance and regulation of inflammation, coagulation and fibrinolysis in the endometrium

Question 4

What are some clinical complications that could occur

Answer 4

Anything different from usual pattern
Too much bleeding - Menorrhagia
Bleeding too often - Polymenorrhoea
IMB / PCB (intermenstrual bleeding, post-coital bleeding) 
Chaotic bleeding

Question 5

How to classify causes of uterine bleeding

Answer 5

Can be acute, intermittent or chronic
Can test the frequency, regularity, duration and volume of bleeding

Structural causes:

Polyp (small benign growth from mucous membrane of endometrium)
Adenomyosis (tissue that normally lines the uterus grows into the muscular walls of the uterus)
Leiomyoma (fibroids, benign extra growth of smooth muscle)
Malignancy

Non structural causes:
Coagulopathy 
Ovulatory dysnfunction
Iatrogenic 
Endometrial
Not otherwise classified

Question 6

Causes of abnormal vaginal bleeding

Answer 6

‘Pathological causes’
Fibroids – submucous
Adenomyosis
Endometrial pathology – benign adenomas or polyps
			             - hyperplasia
			             - carcinoma

Cervical pathology – polyps
			       - carcinoma
Cervical Infection - Chlamydia
Pregnancy!!!
DUB - diagnosis of exclusion

Question 7

Importance of intrauterine submucosal abnormalities

Answer 7

Submucous fibroids (leiomyomas) are associated with a threefold increased risk of abnormal bleeding – invariably menorrhagia
Endometrial Polyps (adenomas) are more frequent in women with menstrual disorders
Causal / casual – diagnostic bias??

Question 8

What are our aims when diagnosing abnormal bleeding

Answer 8

Exclude pregnancy
Exclude cervical pathology
Exclude focal benign intracavity pathology (polyps, submucous fibroids)
Consider other endometrial pathology (> 40)
Use the least invasive method to achieve this

Question 9

What are some examples of endometrial abnormalities

Answer 9

Dysfunctional uterine bleeding
Endometrial polyps
Endometrial hyperplasia
Endometrial hyperplasia with atypia (mild – severe)
Endometrial adenocarcinoma

Of women presenting with menorrhagia 50-60% will have NO structural or obvious pathological cause identifiable – it is a problem at the molecular level i.e. cellular dysfunction

It is a diagnosis of exclusion

Question 10

where is the dysfunction with DUB (Dysfunctional uterine bleeding)

Answer 10

Where’s the dysfunction?
PGs (E + I vs F2a + Tx)
Interleukins (IL – 8, 13 +16)
Tissue Necrosis Factor (TNF) + Platelet Aggregating Factor (PAF)
Matrix metallo-proteinases
Coagulation / fibrinolysis
Junctional zone

Question 11

What are polyps

Answer 11

Benign endometrial adenomas
Focal problem
Rest of endometrium is normal

Question 12

What points to ask in a history examination for abnormal bleeding

Answer 12

Points in history
LMP – was it normal?
Regular or irregular periods
cycle control (ovulation vs anovulation)
heavy- clots, flooding?
with bleeding between (IMB)?
post coital bleeding (PCB)?
Pain
Medication, smoker, smear, operations
Contraception -  hormonal vs non-hormonal 

Points in examination
BMI
Abdomen
Distension, scars, pain, masses
Bimanual 
Uterine size, adnexal masses, pain
Cervix 
polyps, suspect lesions

Question 13

Points to note in abnormal bleeding investigations

Answer 13

Pregnancy test where appropriate
Hb if heavy bleeding
Swabs – endocervical (Chlamydia)
Cervical smear – only if due
Transvaginal ultrasound
\+/- Endometrial sampling
\+/- Hysteroscopy - in-patient or OPD

Question 14

Describe the need for a Transvaginal ultrasound

Answer 14

Can assess the relationship of fibroids to the cavity
Has a high detection rate for polyps
Assess function – anovulatory cycles
Can reliably assess structures outside the uterus (tubal and ovarian pathology)
Well accepted by patients
Relatively cheap with few complications

Periovulatory endometrium is hard to hide pathology in – or immediately post menstrual to assess ET
Cut-off values for ET are arbitrary in premenopausal women - @ 6 mm post menstrual or 12 mm anytime in cycle
Hydrosonography
Ultrasound is ideal for focal pathology but not good for predicting endometrial pathology – a biopsy is still needed in many cases

Question 15

Risk factors for severe endometrial abnormalities

Answer 15

Obesity
Nullipartity
Early menarche / late menopause – length of E2 exposure – weak factor
HT / DM
Anovulation e.g. PCOS
Genetics - FH breast / endometrial / colonic cancer – Lynch syndrome (HNPCC)

Question 16

What is the effect of unopposed oestrogen

Answer 16

Obesity – peripheral conversion of androgen to oestrogen (aromatase)
BMI most vital factor
The more adipose tissue the more conversion to oestrogen

Chronic anovulation e.g. PCOS
Follicular ovarian oestrogen production continues
Progesterone only produced after ovulation
Unopposed oestrogen
Over years leads to hyperplasia and sometimes cancer

Question 17

Describe some treatments for polyps and fibroids

Answer 17

Polyps
Surgery  TCRP
Fibroids
Medical  Mirena IUS
Surgery TCRF/Myomectomy
Hysterectomy 
total/subtotal abdominal
vaginal

Question 18

Treatment options for DUB (dysfunctional uterine bleeding)

Answer 18

Does she need or want treatment?
Does she need contraception/desire pregnancy?
How much is the problem affecting her quality of life?

Nothing
Medical
Non Hormonal (what is the dysfunction????)
Tranexamic acid - anti fibrinolytics 40-50% reduction in blood loss
Corrects excessive fibrin breakdown in endometrium (affects plasminogen action)

Mefanamic acid 30% reduction in blood loss
NSAID – corrects PG imbalance to allow normal vasoconstriction and platelet aggregation
Good for pain also!

Hormonal
Mirena IUS – 90% reduction blood loss
30% amenorrheic
Local high dose progestagen - thin endometrium

COCP – 20 - 30% reduction in blood loss
Removes cyclical events – thin endometrium

Progestagens less beneficial for volume loss
Use to control cycle length in anovulatory DUB

Surgery – for failed medical treatment
Endometrial resection/ablation
Hysterectomy - Vaginal/abdominal
Remove ovaries?

Question 19

Key things to note with endometrial abnormalities

Answer 19

Most menorrhagia is DUB and treatments reflect the dysfunction
Exclude focal pathology – needs focal removal
Beware erratic bleeding – pathology much more likely
TVS and biopsy +/- hysterosocpy diagnosis in nearly all